{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T04:02:36Z","timestamp":1780372956483,"version":"3.54.1"},"reference-count":86,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Global Fund\u2014ENTerritorio","award":["222005"],"award-info":[{"award-number":["222005"]}]},{"name":"Global Fund\u2014ENTerritorio","award":["CI-INS-012-2023"],"award-info":[{"award-number":["CI-INS-012-2023"]}]},{"name":"Global Fund\u2014ENTerritorio","award":["HERMES 58347"],"award-info":[{"award-number":["HERMES 58347"]}]},{"name":"Global Fund\u2014ENTerritorio","award":["60233"],"award-info":[{"award-number":["60233"]}]},{"name":"Universidad Nacional de Colombia","award":["222005"],"award-info":[{"award-number":["222005"]}]},{"name":"Universidad Nacional de Colombia","award":["CI-INS-012-2023"],"award-info":[{"award-number":["CI-INS-012-2023"]}]},{"name":"Universidad Nacional de Colombia","award":["HERMES 58347"],"award-info":[{"award-number":["HERMES 58347"]}]},{"name":"Universidad Nacional de Colombia","award":["60233"],"award-info":[{"award-number":["60233"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Background: The Zika virus (ZIKV) is an arbovirus linked to \u201cCongenital Zika Syndrome\u201d and a range of neurodevelopmental disorders (NDDs), with microcephaly as the most severe manifestation. Milder NDDs, such as autism spectrum disorders and delays in neuropsychomotor and language development, often go unnoticed in neonates, resulting in long-term social and academic difficulties. Murine models of ZIKV infection can be used to mimic part of the spectrum of motor and cognitive deficits observed in humans. These can be evaluated through behavioral tests, enabling comparison with gene expression profiles and aiding in the characterization of ZIKV-induced NDDs. Objectives: This study aimed to identify genes associated with behavioral changes following a subtle ZIKV infection in juvenile BALB\/c mice. Methods: Neonatal mice were subcutaneously inoculated with ZIKV (MH544701.2) on postnatal day 1 (DPN) at a dose of 6.8 \u00d7 103 PFU. Viral presence in the cerebellum and cortex was quantified at 10- and 30-days post-infection (DPI) using RT-qPCR. Neurobehavioral deficits were assessed at 30 DPI through T-maze, rotarod, and open field tests. Next-Generation Sequencing (NGS) was performed to identify differentially expressed genes (DEGs), which were analyzed through Gene Ontology (GO) and KEGG enrichment. Gene interaction networks were then constructed to explore gene interactions in the most enriched biological categories. Results: A ZIKV infection model was successfully established, enabling brain infection while allowing survival beyond 30 DPI. The infection induced mild cognitive behavioral changes, though motor and motivational functions remained unaffected. These cognitive changes were linked to the functional repression of synaptic vesicles and alterations in neuronal structure, suggesting potential disruptions in neuronal plasticity. Conclusions: Moderate ZIKV infection with circulating strains from the 2016 epidemic may cause dysregulation of genes related to immune response, alterations in cytoskeletal organization, and modifications in cellular transport mediated by vesicles. Despite viral control, neurocognitive effects persisted, including memory deficits and anxiety-like behaviors, highlighting the long-term neurological consequences of ZIKV infection in models that show no apparent malformations.<\/jats:p>","DOI":"10.3390\/v17030405","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T04:18:32Z","timestamp":1741839512000},"page":"405","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Mild Zika Virus Infection in Mice Without Motor Impairments Induces Working Memory Deficits, Anxiety-like Behaviors, and Dysregulation of Immunity and Synaptic Vesicle Pathways"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3689-4743","authenticated-orcid":false,"given":"Jaime Alexander","family":"Chivat\u00e1-\u00c1vila","sequence":"first","affiliation":[{"name":"Grupo de Gen\u00f3mica de Microorganismos Emergentes, Direcci\u00f3n de Investigaci\u00f3n en Salud P\u00fablica, Instituto Nacional de Salud, Bogot\u00e1 111321, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Rojas-Estevez","sequence":"additional","affiliation":[{"name":"Grupo de Gen\u00f3mica de Microorganismos Emergentes, Direcci\u00f3n de Investigaci\u00f3n en Salud P\u00fablica, Instituto Nacional de Salud, Bogot\u00e1 111321, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra M.","family":"Mu\u00f1oz-Suarez","sequence":"additional","affiliation":[{"name":"Grupo de Animales de Laboratorio, Direcci\u00f3n de Producci\u00f3n, Instituto Nacional de Salud, Bogot\u00e1 111321, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esthefanny","family":"Caro-Morales","sequence":"additional","affiliation":[{"name":"Grupo de Animales de Laboratorio, Direcci\u00f3n de Producci\u00f3n, Instituto Nacional de Salud, Bogot\u00e1 111321, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aura Caterine","family":"Rengifo","sequence":"additional","affiliation":[{"name":"Grupo de Morfolog\u00eda Celular, Direcci\u00f3n de Investigaci\u00f3n en Salud P\u00fablica, Instituto Nacional de Salud, Bogot\u00e1 111321, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6620-2615","authenticated-orcid":false,"given":"Orlando","family":"Torres-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Grupo de Morfolog\u00eda Celular, Direcci\u00f3n de Investigaci\u00f3n en Salud P\u00fablica, Instituto Nacional de Salud, Bogot\u00e1 111321, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6039-0213","authenticated-orcid":false,"given":"Jose Manuel","family":"Lozano","sequence":"additional","affiliation":[{"name":"Grupo Mimetismo Molecular de los Agentes Infecciosos, Departamento de Farmacia, Facultad de Ciencias, Universidad Nacional de Colombia, Bogot\u00e1 11001, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6534-0079","authenticated-orcid":false,"given":"Diego A.","family":"\u00c1lvarez-D\u00edaz","sequence":"additional","affiliation":[{"name":"Grupo de Gen\u00f3mica de Microorganismos Emergentes, Direcci\u00f3n de Investigaci\u00f3n en Salud P\u00fablica, Instituto Nacional de Salud, Bogot\u00e1 111321, Colombia"},{"name":"Grupo de Investigaci\u00f3n y Desarrollo en Vacunas y Biol\u00f3gicos Estrat\u00e9gicos en Salud P\u00fablica, Direcci\u00f3n de Producci\u00f3n, Instituto Nacional de Salud, Bogot\u00e1 111321, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.3201\/eid1509.090442","article-title":"Zika Virus Outside Africa","volume":"15","author":"Hayes","year":"2009","journal-title":"Emerg. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"55","DOI":"10.15585\/mmwr.mm6503e1","article-title":"Zika Virus Spreads to New Areas\u2014Region of the Americas, May 2015\u2013January 2016","volume":"65","author":"Hennessey","year":"2019","journal-title":"MMWR. Morb. Mortal. Wkly. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.virol.2020.01.015","article-title":"Zika Virus-Spread, Epidemiology, Genome, Transmission Cycle, Clinical Manifestation, Associated Challenges, Vaccine and Antiviral Drug Development","volume":"543","author":"Pielnaa","year":"2020","journal-title":"Virology"},{"key":"ref_4","unstructured":"PAHO\/WHO PLISA Plataforma de Informaci\u00f3n En Salud Para Las Am\u00e9ricas (2023, December 14). Zika\u2014Reporte de Casos Acumulados. Available online: https:\/\/www3.paho.org\/data\/index.php\/es\/temas\/zika-weekly-es\/."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Gasco, S., and Mu\u00f1oz-Fern\u00e1ndez, M.\u00c1. (2020). A Review on the Current Knowledge on Zikv Infection and the Interest of Organoids and Nanotechnology on Development of Effective Therapies against Zika Infection. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010035"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/0035-9203(52)90043-6","article-title":"Zika Virus (II). Pathogenicity and Physical Properties","volume":"46","author":"Dick","year":"1952","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_7","first-page":"20","article-title":"Zika Virus Infection, Basic and Clinical Aspects: A Review Article","volume":"48","author":"Noorbakhsh","year":"2019","journal-title":"Iran. J. Public Health"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1016\/S0140-6736(16)00651-6","article-title":"Association between Zika Virus and Microcephaly in French Polynesia, 2013\u20132015: A Retrospective Study","volume":"387","author":"Cauchemez","year":"2016","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"858","DOI":"10.15585\/mmwr.mm6731e1","article-title":"Vital Signs: Zika-Associated Birth Defects and Neurodevelopmental Abnormalities Possibly Associated with Congenital Zika Virus Infection\u2014U.S. Territories and Freely Associated States, 2018","volume":"67","author":"Rice","year":"2018","journal-title":"MMWR. Morb. Mortal. Wkly. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1056\/NEJMra1808246","article-title":"Zika Virus Infection\u2014After the Pandemic","volume":"381","author":"Musso","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1001\/jamapediatrics.2019.5204","article-title":"Neurodevelopmental Abnormalities in Children with in Utero Zika Virus Exposure Without Congenital Zika Syndrome","volume":"174","author":"Mulkey","year":"2020","journal-title":"JAMA Pediatr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1038\/s41591-019-0496-1","article-title":"Delayed Childhood Neurodevelopment and Neurosensory Alterations in the Second Year of Life in a Prospective Cohort of ZIKV-Exposed Children","volume":"25","author":"Brasil","year":"2019","journal-title":"Nat. Med."},{"key":"ref_13","first-page":"1343","article-title":"Description of 13 Infants Born During October 2015\u2013January 2016 With Congenital Zika Virus Infection Without Microcephaly at Birth\u2014Brazil","volume":"65","author":"Pessoa","year":"2019","journal-title":"MMWR. Morb. Mortal. Wkly. Rep."},{"key":"ref_14","first-page":"2","article-title":"Complete Genome Sequence of a Colombian Zika Virus Strain Obtained from BALB\/c Mouse Brain after Intraperitoneal Inoculation","volume":"8","author":"Rengifo","year":"2019","journal-title":"Microbiol. Resour. Announc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.chom.2016.03.010","article-title":"A Mouse Model of Zika Virus Pathogenesis","volume":"19","author":"Lazear","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.stem.2016.08.005","article-title":"Zika Virus Infects Neural Progenitors in the Adult Mouse Brain and Alters Proliferation","volume":"19","author":"Li","year":"2016","journal-title":"Cell Stem Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3890","DOI":"10.1038\/s41467-019-11866-7","article-title":"Zika Virus Replicates in Adult Human Brain Tissue and Impairs Synapses and Memory in Mice","volume":"10","author":"Figueiredo","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Paul, A.M., Acharya, D., Neupane, B., Thompson, E.A., Gonzalez-Fernandez, G., Copeland, K.M., Garrett, M., Liu, H., Lopez, M.E., and de Cruz, M. (2018). Congenital Zika Virus Infection in Immunocompetent Mice Causes Postnatal Growth Impediment and Neurobehavioral Deficits. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.02028"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Rengifo, A.C., Rivera, J., \u00c1lvarez-D\u00edaz, D.A., Naizaque, J., Santamaria, G., Corchuelo, S., G\u00f3mez, C.Y., and Torres-Fern\u00e1ndez, O. (2023). Morphological and Molecular Changes in the Cortex and Cerebellum of Immunocompetent Mice Infected with Zika Virus. Viruses, 15.","DOI":"10.3390\/v15081632"},{"key":"ref_20","first-page":"208","article-title":"Development of the Human Cerebral Cortex. A Cytoarchitectonic Theory","volume":"29","year":"1999","journal-title":"Rev. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Martynoga, B., Drechsel, D., and Guillemot, F. (2012). Molecular Control of Neurogenesis: A View from the Mammalian Cerebral Cortex. Cold Spring Harb. Perspect. Biol., 4.","DOI":"10.1101\/cshperspect.a008359"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.mcn.2010.05.001","article-title":"Astroglial Cells in the External Granular Layer Are Precursors of Cerebellar Granule Neurons in Neonates","volume":"44","author":"Silbereis","year":"2010","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pneurobio.2013.04.001","article-title":"Brain Development in Rodents and Humans: Identifying Benchmarks of Maturation and Vulnerability to Injury across Species","volume":"106\u2013107","author":"Semple","year":"2013","journal-title":"Prog. Neurobiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"S163","DOI":"10.33588\/rn.41S01.2005374","article-title":"Modelos Experimentales En Ratones Silvestres y Transg\u00e9nicos Para El Estudio de Funciones Motoras y Cognitivas","volume":"41","year":"2005","journal-title":"Rev. Neurol."},{"key":"ref_25","unstructured":"Garber, J., Barbee, W., and Bielitzki, J. (2011). Guide for the Care and Use of Laboratory Animals, National Academies Press. [Eighth ed.]."},{"key":"ref_26","unstructured":"Russell, W., and Burch, R. (1959). The Principles of Humane Experimental Technique, UFAW."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1258\/0023677011911859","article-title":"Use of Score Sheets for Welfare Assessment of Transgenic Mice","volume":"35","author":"Rolls","year":"2001","journal-title":"Lab. Anim."},{"key":"ref_28","first-page":"97","article-title":"Guidelines for the Assessment and Management of Pain in Rodents and Rabbits","volume":"46","author":"Kohn","year":"2007","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"ref_29","unstructured":"Cepeda Prado, E.A. (2003). Diferencias En La Expresi\u00f3n de Marcadores Neuronales y No Neuronales En Cerebros de Dos Cepas de Rat\u00f3n Adulto, Pontificia Universidad Javeriana."},{"key":"ref_30","first-page":"e61922","article-title":"Cerebellar Regional Dissection for Molecular Analysis","volume":"2020","author":"Hamel","year":"2020","journal-title":"J. Vis. Exp."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1038\/nprot.2012.099","article-title":"Culturing Pyramidal Neurons from the Early Postnatal Mouse Hippocampus and Cortex","volume":"7","author":"Beaudoin","year":"2012","journal-title":"Nat. Protoc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"104967","DOI":"10.1016\/j.meegid.2021.104967","article-title":"An Updated RT-QPCR Assay for the Simultaneous Detection and Quantification of Chikungunya, Dengue and Zika Viruses","volume":"93","author":"Rivera","year":"2021","journal-title":"Infect. Genet. Evol."},{"key":"ref_33","unstructured":"La Roche Hoffmann, F. (2003). Creating Standard Curves with Genomic DNA or Plasmid DNA Templates for Use in Quantitative PCR., Applied Biosystems."},{"key":"ref_34","unstructured":"Krueger, F., James, F., Ewels, P., Afyounian, E., Weinstein, M., Schuster-Boeckler, B., Hulselmans, G. (2025, March 09). FelixKrueger\/TrimGalore: v0.6.10\u2014Add default decompression path. Zenodo, Available online: https:\/\/zenodo.org\/record\/7598955."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1093\/bioinformatics\/btp120","article-title":"TopHat: Discovering Splice Junctions with RNA-Seq","volume":"25","author":"Trapnell","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"FeatureCounts: An Efficient General Purpose Program for Assigning Sequence Reads to Genomic Features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Love, M.I., Huber, W., and Anders, S. (2014). Moderated Estimation of Fold Change and Dispersion for RNA-Seq Data with DESeq2. Genome Biol., 15.","DOI":"10.1186\/s13059-014-0550-8"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"W415","DOI":"10.1093\/nar\/gkae456","article-title":"WebGestalt 2024: Faster Gene Set Analysis and New Support for Metabolomics and Multi-Omics","volume":"52","author":"Elizarraras","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING Database in 2023: Protein\u2013Protein Association Networks and Functional Enrichment Analyses for Any Sequenced Genome of Interest","volume":"51","author":"Szklarczyk","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1037\/h0053570","article-title":"Exploratory Behavior and Its Relation to Spontaneous Alternation in a Series of Maze Exposures","volume":"45","author":"Montgomery","year":"1952","journal-title":"J. Comp. Physiol. Psychol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"d\u2019Isa, R., Comi, G., and Leocani, L. (2021). Apparatus Design and Behavioural Testing Protocol for the Evaluation of Spatial Working Memory in Mice through the Spontaneous Alternation T-Maze. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-00402-7"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0149-7634(01)00041-0","article-title":"The Neurobiological Basis of Spontaneous Alternation","volume":"26","author":"Lalonde","year":"2002","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.brainres.2019.01.040","article-title":"GSK3\u03b2 Overexpression Driven by GFAP Promoter Improves Rotarod Performance","volume":"1712","year":"2019","journal-title":"Brain Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Deacon, R.M.J. (2013). Measuring Motor Coordination in Mice. J. Vis. Exp., e2609.","DOI":"10.3791\/2609-v"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/B978-0-444-63956-1.00006-0","article-title":"Physiology of the Cerebellum","volume":"154","year":"2018","journal-title":"Handb. Clin. Neurol."},{"key":"ref_47","unstructured":"(2024, January 12). International Mouse Phenotyping Consorcium Rotarod Protocol. Available online: https:\/\/www.mousephenotype.org\/impress\/ProcedureInfo?action=list&procID=168."},{"key":"ref_48","first-page":"55491","article-title":"Battery of Behavioral Tests Assessing General Locomotion, Muscular Strength, and Coordination in Mice","volume":"2018","author":"Osmon","year":"2018","journal-title":"J. Vis. Exp."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Seibenhener, M.L., and Wooten, M.C. (2015). Use of the Open Field Maze to Measure Locomotor and Anxiety-like Behavior in Mice. J. Vis. Exp., e52434.","DOI":"10.3791\/52434"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Ireland, D.D.C., Manangeeswaran, M., Lewkowicz, A.P., Engel, K., Clark, S.M., Laniyan, A., Sykes, J., Lee, H.N., McWilliams, I.L., and Kelley-Baker, L. (2020). Long-Term Persistence of Infectious Zika Virus: Inflammation and Behavioral Sequela in Mice. PLoS Pathog., 16.","DOI":"10.1101\/2020.06.11.145854"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5393","DOI":"10.1523\/JNEUROSCI.2666-18.2019","article-title":"Mouse Strain and Sex-Dependent Differences in Long-Term Behavioral Abnormalities and Neuropathologies after Developmental Zika Infection","volume":"39","author":"Kramer","year":"2019","journal-title":"J. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/nri3581","article-title":"Regulation of Type I Interferon Responses","volume":"14","author":"Ivashkiv","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1146\/annurev-immunol-032713-120231","article-title":"Interferon-Stimulated Genes: A Complex Web of Host Defenses","volume":"32","author":"Schneider","year":"2014","journal-title":"Annu. Rev. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.coviro.2011.10.008","article-title":"Interferon-Stimulated Genes and Their Antiviral Effector Functions","volume":"1","author":"Schoggins","year":"2011","journal-title":"Curr. Opin. Virol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"8880","DOI":"10.1128\/JVI.00354-15","article-title":"Biology of Zika Virus Infection in Human Skin Cells","volume":"89","author":"Hamel","year":"2015","journal-title":"J. Virol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Magoro, T., Dandekar, A., Jennelle, L.T., Bajaj, R., Lipkowitz, G., Angelucci, A.R., Bessong, P.O., and Hahn, Y.S. (2019). IL-1\u03b2\/TNF-\u03b1\/IL-6 Inflammatory Cytokines Promote STAT1-Dependent Induction of CH25H in Zika Virus\u2013Infected Human Macrophages. J. Biol. Chem., 294.","DOI":"10.1074\/jbc.RA119.007555"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Oyarz\u00fan-Arrau, A., Alonso-Palomares, L., Valiente-Echeverr\u00eda, F., Osorio, F., and Soto-Rifo, R. (2020). Crosstalk between RNA Metabolism and Cellular Stress Responses during Zika Virus Replication. Pathogens, 9.","DOI":"10.3390\/pathogens9030158"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1128\/JVI.02744-14","article-title":"Interferon-Induced Ifit Proteins: Their Role in Viral Pathogenesis","volume":"89","author":"Fensterl","year":"2014","journal-title":"J. Virol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Vladimer, G.I., G\u00f3rna, M.W., and Superti-Furga, G. (2014). IFITs: Emerging Roles as Key Anti-Viral Proteins. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00094"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Mancini, A., Ghiglieri, V., Parnetti, L., Calabresi, P., and Di Filippo, M. (2021). Neuro-Immune Cross-Talk in the Striatum: From Basal Ganglia Physiology to Circuit Dysfunction. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.644294"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.imlet.2021.10.001","article-title":"Neuro-Immune-Metabolism: The Tripod System of Homeostasis","volume":"240","author":"Deshpande","year":"2021","journal-title":"Immunol. Lett."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Watts, M.E., Pocock, R., Claudianos, C., Chowen, J.A., Arevalo, M.A., and Rosenberger, T.A. (2018). Brain Energy and Oxygen Metabolism: Emerging Role in Normal Function and Disease. Front. Mol. Neurosci., 11.","DOI":"10.3389\/fnmol.2018.00216"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1146\/annurev.physiol.65.092101.142131","article-title":"In Vivo NMR Studies of the Glutamate Neurotransmitter Flux and Neuroenergetics: Implications for Brain Function","volume":"65","author":"Rothman","year":"2003","journal-title":"Annu. Rev. Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/j.1750-3639.1999.tb00206.x","article-title":"CNS Cell Populations Are Protected from Virus-Induced Pathology by Distinct Arms of the Immune System","volume":"9","author":"Drescher","year":"1999","journal-title":"Brain Pathol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Suzuki, Y., Lutshumba, J., Chen, K.C., Abdelaziz, M.H., Sa, Q., and Ochiai, E. (2023). IFN-\u03b3 Production by Brain-Resident Cells Activates Cerebral MRNA Expression of a Wide Spectrum of Molecules Critical for Both Innate and T Cell-Mediated Protective Immunity to Control Reactivation of Chronic Infection with Toxoplasma Gondii. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1110508"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/icb.2017.56","article-title":"IFN-\u03b3 Promotes Transendothelial Migration of CD4+ T Cells across the Blood\u2013Brain Barrier","volume":"95","author":"Sonar","year":"2017","journal-title":"Immunol. Cell Biol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Conti, P., Ronconi, G., Lauritano, D., Mastrangelo, F., Caraffa, A., Gallenga, C.E., Frydas, I., Kritas, S.K., Carinci, F., and Gaudelli, F. (2024). Impact of TNF and IL-33 Cytokines on Mast Cells in Neuroinflammation. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25063248"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.tips.2008.06.005","article-title":"Neuroinflammation and Synaptic Plasticity: Theoretical Basis for a Novel, Immune-Centred, Therapeutic Approach to Neurological Disorders","volume":"29","author":"Sarchielli","year":"2008","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Mottahedin, A., Ardalan, M., Chumak, T., Riebe, I., Ek, J., and Mallard, C. (2017). Effect of Neuroinflammation on Synaptic Organization and Function in the Developing Brain: Implications for Neurodevelopmental and Neurodegenerative Disorders. Front. Cell. Neurosci., 11.","DOI":"10.3389\/fncel.2017.00190"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s11910-020-01072-0","article-title":"Congenital Zika Virus Infection: A Review with Emphasis on the Spectrum of Brain Abnormalities","volume":"20","author":"Vhp","year":"2020","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/cr.2016.58","article-title":"Vertical Transmission of Zika Virus Targeting the Radial Glial Cells Affects Cortex Development of Offspring Mice","volume":"26","author":"Wu","year":"2016","journal-title":"Cell Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1007\/s11604-016-0588-5","article-title":"Neuroimaging Findings of Zika Virus Infection: A Review Article","volume":"34","author":"Keshavarz","year":"2016","journal-title":"Jpn. J. Radiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"156327","DOI":"10.1016\/j.cyto.2023.156327","article-title":"Tropism and Immune Response of Chikungunya and Zika Viruses: An Overview","volume":"170","author":"Ravindran","year":"2023","journal-title":"Cytokine"},{"key":"ref_74","first-page":"75","article-title":"Viral and Host Cellular Factors Used by Neurotropic Viruses","volume":"2","author":"Veettil","year":"2021","journal-title":"Mol. Immunol. Neurol. Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1126\/science.aaz2924","article-title":"Structure of V-ATPase from the Mammalian Brain","volume":"367","author":"Abbas","year":"2020","journal-title":"Science"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1016\/j.celrep.2017.07.040","article-title":"The Presynaptic V-ATPase Reversibly Disassembles and Thereby Modulates Exocytosis but Is Not Part of the Fusion Machinery","volume":"20","author":"Kahms","year":"2017","journal-title":"Cell Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3833","DOI":"10.1073\/pnas.0308186101","article-title":"Tandem MS Analysis of Brain Clathrin-Coated Vesicles Reveals Their Critical Involvement in Synaptic Vesicle Recycling","volume":"101","author":"Blondeau","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1083\/jcb.118.6.1379","article-title":"Clathrin-Coated Vesicles in Nervous Tissue Are Involved Primarily in Synaptic Vesicle Recycling","volume":"118","author":"Maycox","year":"1992","journal-title":"J. Cell Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/35044540","article-title":"Accessory Factors in Clathrin-Dependent Synaptic Vesicle Endocytosis","volume":"1","author":"Slepnev","year":"2000","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"106340","DOI":"10.1016\/j.phrs.2022.106340","article-title":"Shank Postsynaptic Scaffolding Proteins in Autism Spectrum Disorder: Mouse Models and Their Dysfunctions in Behaviors, Synapses, and Molecules","volume":"182","author":"Jung","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.brainres.2010.09.026","article-title":"Sociability and Motor Functions in Shank1 Mutant Mice","volume":"1380","author":"Silverman","year":"2011","journal-title":"Brain Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1097\/DBP.0000000000000665","article-title":"The Spectrum of Developmental Disability with Zika Exposure: What Is Known, What Is Unknown, and Implications for Clinicians","volume":"40","author":"Peacock","year":"2019","journal-title":"J. Dev. Behav. Pediatr."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.beproc.2005.11.010","article-title":"Twenty-Three Generations of Mice Bidirectionally Selected for Open-Field Thigmotaxis: Selection Response and Repeated Exposure to the Open Field","volume":"72","author":"Ravaja","year":"2006","journal-title":"Behav. Process."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/7854_2009_7","article-title":"Neuroanatomy of Anxiety","volume":"2","author":"Canteras","year":"2010","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/0166-4328(94)90008-6","article-title":"Thigmotaxis as an Index of Anxiety in Mice. Influence of Dopaminergic Transmissions","volume":"61","author":"Simon","year":"1994","journal-title":"Behav. Brain Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.physbeh.2014.05.006","article-title":"Assessment of Mouse Anxiety-like Behavior in the Light\u2013Dark Box and Open-Field Arena: Role of Equipment and Procedure","volume":"133","author":"Kulesskaya","year":"2014","journal-title":"Physiol. Behav."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/3\/405\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:52:38Z","timestamp":1760028758000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/3\/405"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,12]]},"references-count":86,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["v17030405"],"URL":"https:\/\/doi.org\/10.3390\/v17030405","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,12]]}}}